The rise of diarrheal illnesses in the children of Pakistan amidst COVID‐19: A narrative review

Abstract Background In Pakistan, 74 children out of 1000 lose their lives annually due to diarrheal illness. This commentary addresses the contributing factors aggravating this growing dilemma and the effect of a simultaneous rise in COVID‐19 cases in a healthcare system ready to collapse, along with providing recommendations to alleviate the problems causing this spike in diarrheal cases. Methods This narrative review has emphasized the causes of the spike in pediatric diarrheal illnesses in Pakistan as well as recommendations offered to lessen the burden by incorporating recent literature (n = 68). Tactics to tackle COVID‐19 alongside diarrheal illnesses were also included. Pakistan was chosen to be assessed due to its high burden of child and infant mortality due to preventable causes. Results The provision of safe drinking water, the proper use of Integrated Management of Newborn and Childhood Illnesses (IMNCI), adequate awareness of the benefits of breastfeeding, the use of correct rehydration techniques such as Oral Rehydration Therapy, and the crucial implementation of the EPI vaccination schedule can curb this increase in diarrheal cases. Conclusion The increased prevalence of diarrheal diseases amongst the pediatric population of Pakistan can be attributed largely due to unsanitary drinking water. Emphasis must be put in the provision of safe drinking water. During the first years of life, children can be kept safe from deadly pathogens just by adequate breastfeeding. IMNCI and EPI must also be properly implemented.

treatable and preventable, diarrhea is the cause of death for 2195 children daily around the world, which is more than malaria, AIDS, and measles combined. 2,4 Worldwide, 1 in 9 child deaths are due to diarrheal illnesses and 801,000 children die every year from diarrhea. 4 Diarrhea also reduces the absorption of vital nutrients, and is a leading contributor to malnutrition in children under 5. 2,5 In the early years of life, diarrheal diseases constitute 10-80% of growth retardation worldwide. 6 The predominant cause of acute diarrhea in children is viral infection with rotavirus being the most common cause, accounting for 40% of hospitalizations amongst children under 5. 3,4 Other causes include bacterial infections, lack of proper breastfeeding, contaminated water, antibiotic effects, and parasitic infections. 3 In Pakistan, a country of over 225 million, 60% of infant and child deaths are caused by diarrhea. 7,8 Children under 5 comprise of only 15% of the population, yet make up 50% of the mortality rate. 9 These statistics do not reflect the true situation due to a lack of a functioning disease surveillance system, as well as inadequate data on births and deaths. 10 However, Pakistan has the highest ratio in Asia for infant mortality from diarrhea. 11 The World Health Organization (WHO) has ranked Pakistan 23 in terms of childhood mortality caused by diarrheal illness, with almost 6.4 million cases of pediatric diarrhea annually. 12 Recently, diarrheal cases in the pediatric population have been on the rise throughout the country, with over 2000 children being admitted in the city of Lahore in just one month's time. 13 In the cities of Islamabad and Rawalpindi, hundreds of children are being admitted daily with bouts of acute viral diarrhea. 14 The situation is mimicked in Karachi, where hospitals are witnessing a surge in diarrheal cases, particularly among children between 3 months and 5 years. 15 In 2022, the province of Sindh is witnessing a surge in cholera cases, with 234 confirmed cases reported from January to May. 16 Eighteen of the 27 deaths in Baluchistan were of children under 7 due to the cholera outbreak, as of May 2022. 17 One way to curb this increase in diarrheal diseases especially in children is to establish educational programs throughout schools in Pakistan to enlighten the public about healthy safety measures, and the first step is to adhere correctly to a theory or model of health education. 18 Worldwide, almost 88% of deaths associated with diarrhea were linked to unsafe water amongst other causes. 4 The probability of diarrheal morbidity and mortality is higher among people with lower socioeconomic status and in circumstances of poor personal and substandard domestic hygiene conditions. 19 The poverty rate in Pakistan has been on a continuous rise since the 90 s, with rates of over 32% in 1999 increasing to above 39% in 2020 as estimated by the World Bank. 20,21 Only 20% of the Pakistani population have access to clean water. 11 Fifty percent of all diseases and 40% of all deaths recorded in Pakistan are due to utilization of polluted water. 11 More than 66% of Pakistani households drink water contaminated with bacteria, resulting in rampant diarrheal illness amongst other diseases such as hepatitis. 22 Contaminated water carries various pathogens causing diarrheal disease, including cholera, amoebiasis, gastroenteritis, giardiasis, and campylobacteriosis, to name a few. 23 Another leading contributor to diarrhea amongst infants in Pakistan is the lack of proper breastfeeding. Babies who are breastfed are proven to have stronger immune systems and less diarrheal episodes and gastroenteritis, also known as stomach flu. 24 However, only 37% of Pakistani women breastfeed their infants exclusively for 6 months, and lack of breastfeeding is correlated with a 165% increase in the frequency of diarrheal episodes amongst infants under 6 months. 10,25 In comparison to those exclusively breastfed, infants who were not breastfed are 15 times more likely to lose their lives due to diarrhea. 10 29 In a single day, the ratio reached 5.46% on July 13, 2022. 29 Over 30,000 deaths have been recorded in Pakistan since 2021 due to COVID-19. 30 The pandemic is caused further strain on an exhausted healthcare system, and surges in diarrheal cases throughout the country may push the country's resources to its brink. Thus, this article offers insights into the trials faced by healthcare professionals and the country in eradicating the causes of diarrheal illnesses especially amongst children, while also battling a surge in COVID-19 cases.

| LITERATURE SEARCH
The covariates associated with diarrheal mortality have been classified as unsafe water, lower socioeconomic conditions, poor personal and substandard hygiene conditions, lack of breastfeeding and immunization according to the Expanded Program of Immunization (EPI), and standard management and treatment strategies. Our methods are coherent with the frameworks and models developed in the previously existing literature. [31][32][33][34] Database searches were performed (PubMed and Google Scholar) using the search terms (diarrhea or dysentery) and (children These measurements are required to lessen disease burden. 35 Since the emergence of COVID-19 in December 2019, the whole world remains in a state of turmoil. Strategies to increase isolation by quarantining is a useful model in regulating transmission and swift spread. As people began staying indoors, many educational institutes shut down, which closed the coping source of many students that have numerous personal and familial issues. 36 Recorded data by the National Institute of Health in Pakistan has computed that the COVID-19 outbreak entered Pakistan through international travelers. 37 Lockdowns and restrictions due to COVID-19 may have negatively affected self-esteem, especially in the elderly population.
Group logotherapy has been found to positively affect self-esteem in the elderly. 38

| INCLUSION AND EXCLUSION CRITERIA
Articles were excluded if they were irrelevant, published before 2000, and in languages other than English. Moreover, articles pertaining to countries other than Pakistan were excluded, along with those that were not associated with the keywords.
Any study found in the literature search was included (reviews or original articles, such as observational or cross-sectional studies). The studies meeting the childhood diarrhea definition of three or more watery or abnormally loose stools within the previous 24 h in a child younger than 5 years of age were taken into consideration.

| DISCUSSION
There are several ways to combat deaths in infants caused by diarrheal illnesses. Amongst the most vital is vaccination against common diarrhea-causing organisms. For example, Rotavirus is one of the most common causes of diarrheal related deaths in infants, which is why vaccines have been developed against it and are approved in almost 200 countries. 39 Another important reason for urgency in combatting these infectious diseases is the overwhelming percentage of children inhabiting developing countries like Pakistan; developing countries are comprised of 85% of the world's young population. 40 Pakistan being a third world nation faces its own set of challenges when it comes to achieving herd immunity against infectious agents. Along with being incapable of affording the correct number of vaccines to fulfill the country's requirements, it also lacks facilities to store and transport them to remote rural areas. 41 Increasing resource depletion which is demonstrated by resource reduction is not just a problem in Pakistan, in fact, it is a worldwide phenomenon. 42 Just as food products must be safe for consumer usage, the proper storage, transfer, and utilization of vaccines is crucial for health. 43 Moreover, this dilemma is aggravated by hoarding of vaccines by developed countries of the world, automatically creating a shortage in chain supply. 44 Studies have been carried out for creating vaccine equality among nations via vaccine empathy and diplomacy, which involves vaccine donations from the privileged nations to the needy. 45 While vaccine empathy can help Pakistan achieve its goals of reducing death tolls from diarrheal diseases, it comes at a price of some unfavorable conditions or sanctions imposed on the country. 45 Moreover, this benevolence from donor nations may come with a price tag of favors that may become a burden on the deteriorating economic situation of the country 45 Furthermore, even after receiving the required number of dosages, the country might lack proper technology (reliance on sophisticated freezers) to store and transport the vaccines. 45 In addition, the correct use of social media platforms can aid in reducing the incidence of diarrheal disease in children. These platforms have steadily gained popularity worldwide and Pakistan remains no exception to it. With this tremendous reach, social media can be used educationally by the health sector of government to control disease spread. From running educational and awareness campaigns to educating people about the severity of the disease, this tactic could reach more people than any other strategy. Discussions on how something considered as a casual stomach upset can transform into a deadly diarrhea, and how easily and quickly children can go into extreme states of dehydration that can cost them their lives. Furthermore, small educational videos can be run as ads on social media as government's public service message on basic first aid treatments to prevent progression to severity. 46 This approach can also curb the challenge of delivering educational messages during COVID-19 lockdowns, since face-to-face classes may be suspended. 47 However, lack of monitoring on social media can prove to be harmful rather than beneficial. One prime example of this occurred in recent monsoon season in Pakistan where dengue was on the rise.
False information regarding papaya leaf juice extract to be the cure of dengue as widely publicized on social media with no proof or scientific backup. The home remedy was readily adopted in many suffering households and resulted in several patients almost collapsing in hospitals due to severe diarrhea from the extract that caused extensive fluid. 48 Therefore, correct usage and management of information spread on social media platforms is critical to achieve the desired goal of a healthier population. In addition, the use of For every 1000 babies born in Pakistan in 2020, 65 don't make it to their 5th birthday. 63 One major cause of infant mortality is inadequate breastfeeding. Breastfeeding is widely accepted as a vital protector against various harmful pathogens, especially for the first months of life. The American Academy of Pediatrics recommends breastfeeding for the first 6 months, and the most recent updates have extended the recommendation until the first 2 years of life. 64 Antibodies against pathogens that the mother and baby have been This pathogen is transmitted by a foodborne route, commonly transmitted through raw or contaminated milk, and the study found that breastfed infants were at a significantly lower risk of enteric infection. 67 They concluded by stating consistent findings with other reports of reduced incidence of diarrhea amongst breastfed children. 67 The recent surge of diarrheal cases in Karachi is believed to be due to using unsterilized water bottles or using contaminated water to make feeders, since most of the patients are between the ages of 3 months and 5 years, when bottle-feeding is common. 15 The use of boiled water for preparation of formula milk remains relatively low, at less than 32% in one study. 67 Along with respiratory infections, diarrhea is one of the leading causes of antibiotic use in children in low and middle-income countries such as Pakistan. 68 Misusing antibiotics to cure diarrhea increases resistance to drugs by different pathogens (bacteria, viruses, or parasites alike), leading to lack of effectiveness and eradication. The lax practice of some healthcare professionals in prescribing unneeded antibiotics, as well as a general increase in selfmedication in Pakistan, is harboring a spike in drug resistant organisms, especially those that cause diarrhea. 69 Globally, Pakistan is ranked third with the most unvaccinated children. The consequences of this shortcoming are apparent, as the country has the third-highest burden of child mortality in the world. 9 The EPI was launched in Pakistan in 1978, and provides protection from deadly yet preventable childhood diseases such as Tuberculosis, Diphtheria, Rotavirus, and Poliomyelitis. 9 In Pakistan, rampant vaccine hesitancy and barriers to provide vaccinations have deprived about 3 million Pakistani children annually from acquiring a full course of childhood vaccinations, despite it being widely available.
One major reason for vaccine hesitancy amongst parents was vaccine hesitancy, with one poll depicting 77% of parents expressing concerns regarding childhood vaccines. 9 However, the true efficacy of the EPI is not apparent due to a lack of proper surveillance systems. One study found that children who have received the Rotavirus vaccine have not shown to have acquired any severe form of rotavirus gastroenteritis, and worldwide, the Rotavirus vaccination prevented 91% of rotavirus infections within the first year of life. 70 To make matters worse, a common clinical presentation of COVID-19 in children is diarrhea, which may present with or without respiratory symptoms. 71 The clinical presentations of various diarrheacausing pathogens mimic COVID-19 and may cause clinical misdiagnosis. Therefore, it is recommended to test for COVID-19 in patients that are presenting with gastrointestinal symptoms. 72 However, an inadequate testing capacity along with a surge in COVID-19 cases daily will prove arduous in the correct diagnosis and treatment of patients, especially children, presenting with diarrhea. 29,73 In the past few years however, the prevalence of diarrhea has changed very little across Pakistan and management of the disease has brought a significant amount of reduction in childhood mortality.
One study measured the prevalence of childhood diarrhea and pneumonia 15 years after introducing improved sanitation, safe drinking water, and engagement between healthcare workers and the community in a rural village of Pakistan. They reported a fourfold decrease in childhood mortality overall and a twofold decrease in morbidity due to diarrhea and pneumonia due to improvements in water quality, sanitation, and housing. 74 The provision of safe drinking water is key to reduce childhood mortality due to diarrhea. Protection from pollutants, chlorination and boiling of water, distribution system integrity, and hygiene are vital practices to reduce mortality. 75,76 Boiling water is microbiologically effective in eradicating diarrhea-causing organisms including vibrio cholerae, G. lamblia, Cryptosporidium parvum, rotavirus, and salmonella typhi. 77 Mothers should be encouraged to use boiled water for preparation of formula milk to reduce the prevalence of diarrhea amongst bottle-fed children. 67 Approximately $442 million worth of funds were also approved by the World Bank in 2021 to enhance the sanitation services of Pakistan. The Punjab Rural Sustainable Water Supply and Sanitation Project aims to increase accessibility to clean water for more than six million rural residents who are deprived of it. 78 Since the province of Sindh holds the highest record of childhood fatality due to diarrhea, it is the most important province to begin improving sanitation services. However, implementation of IMNCI has been subpar in Pakistan, mainly due to the long training duration. 80 A stronger approach to the widespread assimilation of IMNCI into all hospitals and rural areas must be implemented to reap the full benefits of this program. This will require clinical mentoring, adequate supplies and medication, as well as supportive supervision. 80 To combat the surge in COVID-19 cases and to prevent misdiagnosis, adequate provision of testing equipment as well as personal protective equipment are essential. In addition, healthcare workers must be adequately trained in offering breastfeeding counselling to mothers instead of opting to prescribe formula milk.
Pakistan ranks at 18% for the early initiation of breastfeeding and lack of participation in breastfeeding has increased the number of stunted Pakistani children to 44%. 25 Healthcare professionals must also practice calculated use of antibiotics to decrease the chances of drug resistance pathogens that cause diarrhea.
Among the successful treatment interventions of diarrhea, ORS tops the list. 81 One study found that 72.1% of Pakistani mothers have used ORS for diarrhea, indicating its wide use in society. 82 However, preparation of ORS requires accuracy, and is therefore misused by many. 83 Hence, concerted awareness campaigns should be organized to educate parents to practice the correct use and method of utilizing ORS. 82 Antimicrobials, zinc, and vitamin A supplementations have proven beneficial as well. 81 However, many supplements are not widely available in pharmacies across the country. 83 To alleviate this problem, UNICEF along with the Bill and Melinda Gates Foundation have invested over 12 million dollars for supplying medications and commodities and training staff for the treatment of childhood diarrhea and pneumonia. Districts from Sindh and Punjab were selected to have uniform representation. 12 An evaluation 1 year later describes the project as successful, as 22,700 lady healthcare workers were trained in use of commodities in Sindh. 12 The Punjab government intends to invest in it further to increase the project's span up to 10 more areas across the province. 83 In low-income countries, eating healthy is considered no less than a luxury. Vegetable and fruit prices have soared while high fat, sugary junk foods have become cheaper, compelling people to choose the unhealthy option Households in Pakistan spend about two-thirds of their income on food compared with 13% in high income countries. 84 Since an ounce of prevention is better than a pound of cure, the government should enhance the availability and affordability of fruits and vegetables to decrease the population's consumption of unhealthy food sources. Nutritional therapy such as including complex carbohydrates, yogurt, fruits, and vegetables should be popularized through campaigns to confer strong immunity. 81 In addition, changes to the overall economy must be implemented by the introduction of jobs to boost the population's purchasing power since the primary barrier for not seeking hospital care was unaffordability (53%). 85 Recently, EPI Pakistan has successfully added new vaccines and raised coverage to over 80% of population. 86,87 To enhance EPI services in Pakistan, offering regular EPI services throughout all existing health facilities, establishing an EPI center in all union councils, redistributing available vaccinators, and involving all trained manpower for vaccination will increase public access and compliance to the service and thus raise coverage significantly. 87 The government must promote EPI awareness campaigns and advertisements regarding diarrhea's prevention and management to educate the masses and remove misinformation (Table 1). 86

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
All data are available in the manuscript.

TRANSPARENCY STATEMENT
The lead author Mohammad Yasir Essar affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.